The power of peptides

Bolstered by the support of a new grant from the National Institutes of Health (NIH), Research Assistant Professor Jennica Zaro of the USC School of Pharmacy, will be examining the differences between normal cells and tumour cells - one of the biggest challenges encountered by researchers in cancer diagnostics and therapeutics.

The NIH's National Cancer Institute has awarded Zaro a two-year grant totaling $348,272 for a project titled ''Mildly Acidic Tumor Microenvironment for Diagnostic and Therapeutic Nanomedicine.'' The project will focus on breast cancer but is applicable to most other cancers.

Zaro's research expands on current knowledge that areas near tumours are mildly acidic, a well-known fact that has yet to be fully exploited.

''Targeting a mildly acidic range is not a new area of study, but we're doing it differently,'' she explained. ''In our approach we're using small peptide sequences, which become activated in even mildly acidic (low pH) environments.''

The lab work relies on small peptide sequences that are very sensitive to the pH range that exists near solid tumour cells. Using nanotechnology, Zaro has created a specific masking sequence of amino acids that will prevent the peptides from entering healthy cells while allowing them to enter or bind to tumor cells.

When just circulating along normal cells, these peptide sequences do not enter or bind to the cell, but when they enter lower pH areas, they activate the peptide carrier, resulting in surface binding to tumor cells and higher cell internalization.

''The project will pursue two parallel tracks,'' Zaro said. ''The first is to use these peptide sequences as diagnostic imaging agents to locate the cancer cells. Then we can optimise the carrier to deliver a therapeutic agent to these cells for treatment.''

This method is more precise than others that are not able to recognise the small differences in pH levels near tumour cells. As a result, tumor cells in mildly acidic areas are often missed. Since it is more sensitive in mildly acidic environments, Zaro's structure overcomes this shortfall.

Another advantage is that because the body is used to degrading these particular peptides, utilising them to target and treat cancer shouldn't have long-term side effects.

The NIH R21 grant builds on previous financial support Zaro received from the USC Ming Hsieh Institute for Research on Engineering-Medicine for Cancer. The new funding will be used to see if her methods can be effective when applied in vivo.

''Overall, we are trying to understand cancer cells and why they keep growing, and to use that information to prevent and treat cancer,'' Zaro said.